This article is a must read for all women, especially those over 35 years old, who desire become pregnant now or at some time in the future.

In my September 2007 newsletter, I reviewed the association of DNA oxidation with the development of Down's syndrome. In that issue, I also discussed a simple urine test for measurement of DNA oxidation, with a brief discussion of preventive measures for Down's syndrome (DS) in utero.

In this article, I will review the association of maternal thyroid gland dysregulation with the in utero development of DS, and I will conclude with practical steps for preventing maternal thyroid dysregulation resulting in possible prevention of DS.

To understand the importance of proper maternal thyroid function on the developing baby, you need to understand basic thyroid function.

Thyroid Function

Pituitary Gland Control of the Thyroid

One of the many hormones released by the pituitary gland in your brain is called Thyroid Stimulating Hormone (TSH), aka thyrotropin. TSH travels in the blood to the thyroid gland and stimulates the thyroid gland to release thyroid hormones.

Thyroid Hormones: A Numbers Game - T4, T3, T2, rT3

The thyroid gland is located in the neck under the Adam's apple. It produces the hormones T4 (the short name for tetra-iodothyronine, aka thyroxin), T3 (the short name for tri-iodothyronine), rT3 (the short name for reverse-T3) and a tiny bit of T2. 90% of thyroid hormone made is T4. T4 is a pre-hormone and does little until it is activated within our body’s cells. About 10% of thyroid hormone made is T3. T3 is the active form of thyroid hormone and is five times more powerful than T4. Most of the active thyroid hormone our body uses each day is from our body’s cells converting T4 to T3.

rT3's function is analogous to the brakes on your car. rT3 puts the “brakes” on the conversion of T4 to T3 if too much T3 is made under present conditions. In times of severe stress, rT3 is a protective mechanism which slows our metabolism so a person can survive longer without food or water. With prolonged stress, maladaptation can occur with too much rT3 produced, resulting in hypothyroidism. There are other mechanisms by which hypothyroidism can occur, but for this discussion we are focusing on only a couple of mechanisms.

Cell Receptivity to Thyroid Hormones and Genetic Expression

Every cell in the body has a cell nucleus. The nucleus contains the DNA of the cell. DNA is the key component in genetic functions of a cell. Receptors for thyroid hormones are on the cell nucleus. In simple terms, the nuclear receptors’ function is to allow the thyroid hormones to read the instructions to the DNA so the DNA will carry out the functions in the cell. When the DNA has received the instructions and the thyroid hormones functions on the cell are manifested, then we say there is genetic "expression" of thyroid hormone function. There are various types of nuclear receptors to thyroid hormones, and the number of the receptors can vary. Under certain conditions, such as chronic stress, nuclear receptors can be resistant to thyroid hormones. With "unreceptive" receptors, even though the body may produce enough thyroid hormones, low thyroid function can result. It is analogous to a woman who is not receptive to the actions of a man showing interest in her... no matter how much he tries to gain the affection of the woman, if she isn't receptive to him, she won't “express” any interest.

When the Thyroid Goes Wild (... and its partner the Adrenal)

Thyroid dysfunctions are related not only to the thyroid gland itself, but also to a range of secondary metabolic factors associated with poor nutritional status and unhealthy aging. A common association is adrenal gland dysfunction which alters thyroid gland function. This is often seen in women having difficulty becoming pregnant, pregnant women over 35, new mothers and the elderly. Many times what goes wacky first are the adrenal glands, then the thyroid.

Adrenal gland function is most accurately evaluated with samples of adrenal hormones taken from a person’s saliva. This is called the “salivary hormone testing”. Conventionally, blood cortisol levels are used to test adrenal gland function. If that test shows a low or high normal or is slightly out of normal range, the Adrenocorticotropic Hormone (ACTH) stimulation test (via blood testing) is used to check the pituitary glands effect on adrenal function. The problem is the ACTH stimulation test is often normal until the adrenal glands are almost non-functional. Therefore, a person’s adrenal function is often declared “normal” even when it is not functioning well.

Salivary adrenal testing gives more accurate information of the adrenal's function because it measures the more normal day to day function of the adrenal glands the levels at key points throughout an entire day.

All of the hormones associated with thyroid function can be accurately measured in the blood. Most of these blood hormone levels are relatively constant during the day, but there are fluctuations based on the time of day. With TSH, the peak occurs during the night and the low occurs between 10 am to 4pm.1 Thus, to get a relatively stable baseline measurement it is best to measure thyroid-associated hormone levels in the middle of the day. If you are unable to measure mid-day, at least have the blood levels measured at the same time of day for comparison testing.

Often, many doctors screen for thyroid problems with TSH only. In addition, measuring a full functional thyroid panel (TSH, total T3, free T3, free T4, and reverse T3) is often expensive. Sometimes, when only TSH is screened, misdiagnosis could occur. Ultimately, misdiagnosis would be more expensive and more challenging for the person, her child and the rest of the family. As you will soon see, we better check more than TSH because we may miss many problems, thus, possibly affecting the entire life of a child!

Summary of Thyroid Function

In summary, the basic function of the thyroid gland is that of a thermostat for our metabolism.

More importantly, the thyroid hormones, particularly T3, influence proper function of the mitochondira, the cells’ power plants. Without good mitochondrial function the cells will not have energy to carry out their functions. Thus, all cells in the body are affected by the thyroid gland's effects on metabolism.

What are the effects of maternal thyroid function?

Fetal Brain Development

Thyroid hormones are intricately involved in the development of the nervous system in the fetus, in newborns and children. Hypothyroidism in pregnant women and newborns has potential lifetime impacts on the child’s cognitive function, speech, hearing, coordination and behavior.2 Also, T3 stimulates genes that regulate processes of growth of the brain's physical structures.3

Is there a connection with maternal gluten sensitivity and Down Syndrome (DS)?

Down Syndrome and Thyroid Auto-antibodies

First , let me define the term “Thyroid Auto-antibodies”. These are antibodies that attack a person’s own thyroid gland.

Down syndrome children have a congenital gut (gastrointestinal tract, aka GI tract) abnormality called Celiac disease which results in food intolerances to gluten. There are many people who have gluten sensitivities, but Celiac disease is the most severe case of gluten sensitivity/intolerance manifestation at the end of the continuum from sensitivities to intolerances. The congenital gluten intolerances in DS suggest a potential connection between gluten sensitivity and thyroid auto-antibodies. Auto-antibodies to the thyroid gland are one of many results of gluten sensitivities or intolerances. A 2001 study suggests that the effect of dietary antigens, such as those produced by gluten sensitivity or intolerance may be the stimulus for altered immune responses resulting in impaired brain development and cognitive performance in DS.4

Maternal thyroid auto-antibodies could be a trigger for the genetic chromosomal abnormality in the fetus manifesting as DS. It is established that thyroid hormones are intricately involved in the development of the nervous system of the fetus. Thyroid disorders from auto-antibodies to the thyroid are prevalent in adults with Celiac disease. A 2001 study in The American Journal of Gastroenterology reports there is a high prevalence of thyroid disorders in untreated adult Celiac disease patients and that gluten withdrawal may single-handedly reverse the disease.5 Additionally a 1999 article describes a woman with reversal of Hashimoto's thyroiditis when gluten was withdrawn from the diet.6 Therefore, pre-pregnancy gluten withdrawal in those women with either gluten sensitivities or Celiac disease may prevent the chromosomal abnormality resulting in DS.

Down Syndrome Children Have High Thyroid Auto-antibody Levels

Even though DS is a genetic disorder, there is further evidence supporting the possibility of prevention of DS by pre-pregnancy maternal gluten withdrawal in women with gluten sensitivities. Throughout the clinical literature it is well established that DS children commonly have high levels of thyroid auto-antibodies.antibodies.7,8 Could this be the result of in-utero DNA damage as a result of maternal gluten sensitivity from thyroid auto-antibodies?

Is impaired xenoestrogen detoxification associated with thyroid dysfunction?

Almost everyone has Toxic Xenoestrogens

In my June 2007 newsletter, we discussed the effect xenoestrogens have on breast cancer development. Xenoestrogens (pronounced "zee"-"no"-"estrogens") are defined as synthetic substances commonly found in the environment of modern society that differ from those produced by living organisms that have estrogen-like effects. According to government sanctioned research, almost 100% of the U.S. population has at least five of these xenoestrogens in their tissues.

Xenoestrogens Impair Thyroid Function

Many xenoestrogens induce increased phase I detoxification activity. Studies suggest that the toxins dioxin, PBDE's and other xenoestrogens contribute to faster rate of clearance of thyroid hormone from the body, increasing the need for the thyroid gland to produce more to maintain normal tissue levels.9 As more thyroid hormone is cleared faster than it can be made by the thyroid, blood T4 and T3 levels will decrease.10 The bottom line is, with imbalanced detoxification, the cells have less available thyroid hormone.

Impaired Thyroid Function and Down Syndrome

As previously mentioned, thyroid hormones are intricately involved in the development of the fetal nervous system. With less maternal thyroid hormone available this too could be a mechanism resulting in chromosomal abnormalities underlying DS.

What steps can a woman take to prevent maternal thyroid dysfunction?

Women desiring to become pregnant, especially those who are over 35 years old, should consider taking the following steps to prevent thyroid dysfunction during pregnancy:

1. Improve xenoestrogen detoxification. A detoxification program focused on improving balanced phase I and phase II detoxification has a profound effect on not only thyroid dysfunction, but also gut dysfunction, loss of excess fat, and helps balance multiple hormones. Many of my patients start on a one week detoxification program because most people feel significant decrease in severity of symptoms, significantly increased energy, and almost everyone has a permanent loss of 6 to 8 pounds of mostly fat with much of it from their waist. This helps "jump start" the healing responses and motivates people to continue the program.
2. Get adequate nutrient precursors for T4 formation. Iodide is a limiting nutrient in the production of T4. Sea vegetables, such as seaweed, have organic iodide.
3. Decrease thyroid auto-antibodies. As previously discussed, gluten is associated with autoimmune hypothyroidism. Elimination of foods containing gluten and also dairy proteins containing casein decrease the potential for maternal thyroid dysfunction.
4. Improve conversion of T4 to T3. Selenium in the form of selenium methionine is essential to this conversion. 200 mcg is advisable for most people. One big handful of raw brazil nuts has about the same amount of selenium. For people with severe thyroid problems, supplementing with selenium is often necessary.
5. Enhance T3 influence on mitochondrial energetics. Selenium in the form of selenium methionine improves the production of T3 and lowers thyroid auto-antibodies.
6. Improve T3 receptor binding. The cell nuclear receptors interact with vitamin A, conjugated linoleic acid (CLA), and the omega-3 fats, EPA and DHA. Rosemary extract has found to potentiate the effects on vitamin D. Zinc in the form of zinc glycinate promotes proper thyroid function through its role as a cofactor for the thyroid receptor of the cell nucleus. Grass-fed free-range beef is a good food source of CLA. Krill oil or fish oils are high in EPA and DHA. Fatty fish like salmon have significant EPA and DHA.
7. Influence all of the above functions with a consistent combination of resistance and aerobic exercise.

Copyright © 2009; Douglas Husbands, DC, CCN, ABAAHP. All rights reserved.

References

1 Brabant G, Prank K, Hoang-Vu C and von zur Muhlen A. Hypothalamic regulation of pulsatile
thyrotropin secretion. J Clin Endocrinol Metab 1991;72:145-50.
2 Chan S, Kilby M. Thyroid hormone and central nervous system development. J Endocrinol. 2000;165:1-8.
3 Strait K, Carlson D, Schwartz H, et al. Transient stimulation of myelin basic protein gene expression in differentiating cultured oligodendrocytes: a model for 3,5,3'-triiodothyronine-induced brain development. Endocrinology. 1997;138:635-41. (http://endo.endojournals.org/cgi/content/full/138/2/635)
4 Licastro F, Mariani R, Faldella G, et.al. Immune-endocrine status and coeliac disease in children with Down's syndrome: relationships with zinc and cognitive efficiency. Brain Res Bull. 2001;55:313-17.
5 Sategna-Guidetti C, Volta U, Ciacci C, et al. Prevelance of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Am J Gastroenterol. 2001;96:751-57.
6 Valentino R, Savastano S, Tommaselli A, et al. Unusual association of thyroiditis, Addison's disease, ovarian failure and celiac disease in a young woman. J Endocrinol Invest. 1999;22:390-94.
7 Rooney S, Walsh E. Prevalence of abnormal thyroid function tests in a Down's syndrome population. Ir J Med Sci. 1997:166:80-82.
8 Kanavin O, Aaseth J, Birketvedt G, Thyroid hypofunction in Down’s syndrome: is it related to oxidative stress? Biol Trace Elem Res. 2000;78:35-42.
9 Fletcher N, Geise N, Schmidt C, et al. Altered retenoid metabolism in female Long-Evans and Han/Wistar rats following long-term 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD)-treatment. Toxicol Sci. 2005;86:264-272.
10 Van Birgelen A, Van der Kolk J, Fase K, et al. Subchronic dose-response study of
2,3,7,8-tetracholorodibenzo-p-dioxin in female Sprague-Dawley rats. Toxicol Appl Pharmacol. 1995;132:1-13.

Author's Bio: 

Dr Husbands has been helping people resolve chronic health problems and improve their health for over two decades. He is a natural healthcare physician in the San Francisco Bay Area. He graduated from San Francisco State University with a Bachelor of Science degree in Biology/Human Physiology in 1983. In 1991, he graduated from Cleveland Chiropractic College of Los Angeles and became a Doctor of Chiropractic. In 1996, he earned his post-graduate board certification as a Certified Clinical Nutritionist with the International and American Associations of Clinical Nutritionists, and in 2000, he became a certified Anti-Aging Health Care Practitioner with the American Board of Anti-Aging Health Practitioners. In 2003, he completed training in Functional Medicine with the Institute for Functional Medicine. Dr. Husbands has been sought for expert opinion by national health magazines and been published in peer-reviewed journals. He has taught many classes and lectured extensively to a wide variety of audiences on natural health topics and functional medicine. He sees patients at the Athens Chiropractic Clinic in San Carlos, CA. He offers phone consultations for those who live outside of the area. Find out more about Dr Husbands at www.drhusbands.com.